肺岩宁对Lewis肺癌荷瘤小鼠瘤组织中核小体构象调控因子H3-K56、Rtt109、Asf1及E2F1表达的影响

Effects of Chinese herbal medicine Feiyanning decoction on expressions of nucleosome conformation-regulating factors H3-K56,Rtt109,Asf1 and E2F1 in Lewis-bearing mice

目的:恶性肿瘤细胞具有异常的细胞周期。前期体内实验证实肺岩宁具有干预细胞周期G_1/S检测点信号通路的作用,本研究进一步探讨肺岩宁对S期核小体构象调控因子表达的影响。方法:将60只小鼠随机分成正常组、模型组、顺铂组和肺岩宁组,每组15只。右腋部皮下注射Lewis细胞构建C57BL/6小鼠Lewis肺癌移植瘤模型。观察各组小鼠的瘤质量和抑瘤率,采用流式细胞术检测细胞周期时相分布和增殖指数,实时聚合酶链反应法及蛋白质印迹法检测各组小鼠肺癌移植瘤细胞的核小体构象调控因子H3-K56、Ty1转座基因调节因子109(regulator of Ty1 transposition 109,Rtt109)、细胞反沉默功能因子1(antisilencing function1,Asf1)、腺病毒E2启动子结合转录因子1(E2F1)mRNA和蛋白的表达。结果:肺岩宁组和顺铂组的瘤质量显著低于模型组(P<0.01),抑瘤率分别为27.92%和42.50%。肺岩宁组癌细胞的增殖指数明显低于模型组和顺铂组,S期分布比例最少(P<0.01)。肺岩宁组H3-K56、Rtt109、Asf1、E2F1 mRNA和蛋白的表达较模型组显著下调(P<0.05)。结论:肺岩宁可能是通过影响核小体构象调控因子的表达干预异常细胞周期来发挥抗肺癌细胞生长增殖作用。

OBJECTIVE： Malignant tumor cells were found with an abnormal cell cycle. Previous in vivo experiment had confirmed the Feiyanning＇s intervention effect on checkpoint signaling of G1/S in the cell cycle. This study was to further observe the expressions of nucleosome conformation-regulating factors intervened by Feiyanning decoction in S phase. METHODS. Lewis lung carcinoma models of C57BL/6 mice were established. Sixty mice were randomly divided into four groups, normal control group, model control group, Feiyanning group, and cisplatin group. There were 15 mice in each group. Tumor weight and tumor inhibition rate were observed. In addition, the cell cycle distribution was detected by flow cytometry and the proliferation index was calculated. Furthermore, mRNA and protein expressions of H3-K56, regulator of Tyl transposition 109 （Rttl09）, antisilencing function 1 （Asfl） and E2F] were analyzed by real-time polymerase chain reaction and Western blot methods, respectively. RESULTS ： The tumor weights of mice in the Feiyanning group and the cisplatin group were lower than those in the model group （P〈0.01）, with tumor inhibition rates of 27.92% and 42.50%, respectively. Cancer cell proliferation index and proportion of cancer cell population in S phase in the Feiyanning group were significantly lower than those in thecisplatin group （P〈0.01）. The mRNA and protein levels of H3-K56, Rttl09, Asfl, E2F1 in the Feiyanning group were lower than those in CONCLUSION： Feiyanning plays a role in intervening regulating factors and thus inhibits the lung cancer cel the model group （P〈0.05）. n the abnormal cell cycle by nucleosome conformation- proliferation.